Background: Antimicrobial use in companion animals could be an overlooked contributor to antimicrobial resistance relevant to human health. The aim of this study was to describe the material, biotic, and infrastructural interdependencies involved in antimicrobial use in the veterinary care of UK companion animals, particularly dogs. Methods: Veterinary clinics, the main site of decision-making regarding companion animal antimicrobial use, are the focus of this mixed-methods thesis. Highest priority critically important antimicrobial (HPCIA) dispensing data were analysed using a mixed-effect, hierarchical modelling approach (dogs nested in clinics nested in veterinary groups). Ethnographic fieldwork in three veterinary clinics lasting nine months explored the animal–human–microbe interactions at play and situated these within wider political and economic contexts of the companion animal veterinary sector. Observations, interviews, and documentary analysis were undertaken and synthesised using a comparative approach. Findings: Records of 468,665 antimicrobial dispensing events were analysed. Differences in the odd ratios of an event comprising of a HPCIA were apparent between veterinary groups (ranging from 1.00 to 7.31, 95% confidence interval 5.14–10.49). Fieldwork identified the infrastructural arrangements that support current patterns of antimicrobial use including the ‘business model of busyness’ and the role of the veterinary-industrial complex. Interspecies care involved the entanglement of mammalian and microbial bodies and was delivered within temporal and logistical constraints, at times in tension with infection control procedures. Antimicrobials formed part of the veterinary care for socially desirable—yet inherently unhealthy—breeds of dog. Conclusions: Antimicrobial use is a bio-social practice that is produced by social, material, semiotic, and technical networks extending beyond the actors at the interface of their deployment. By rendering visible these networks—and decentring human behaviour as the focus for efforts to address antimicrobial use—this thesis proposes alternative approaches to reduce the pressures to prescribe antimicrobials in companion animals.